Author

Dudasova, Anita

Attention

2299/3638

Abstract

Although there is a renewed interest in the therapeutic potential of cannabinoids, pharmacological and physiological characterisation of these promising compounds is currently not well documented in the respiratory system. The aim of this study is to increase our understanding of possible roles of cannabinoids in the airways. Apart from CB1 and CB2 receptor-mediated actions, cannabinoid compounds can also target TRPV1 receptors, ion channels or the orphan GPR55. In isolated guinea-pig bronchi, WIN55212-2 probably exerted its inhibitory effect on sensory nerves through CB2-like receptors. VIR did not act prejunctionally but its excitatory action was mediated through TRPV1 receptors. Δ9-THC activated sensory nerves presumably involving CB1 receptors. It was speculated that GPR55 might be activated by VIR and antagonized by CBD. CBD revealed multiple mechanisms of actions: it antagonized effects mediated by TRPV1 and NK2 receptors, modulated mast cell function and showed anti-allergic activity in an in vitro model of bronchial asthma. In a human bronchial epithelial cell line the functional expression of CB1 receptors could not be confirmed. Cannabinoids examined in this study were ineffective to induce signal transduction which would be linked to ion channel activity or to intracellular Ca2+ changes. Only VIR might trigger a CB1 receptor-independent signalling pathway in these cells. In conclusion, the findings presented in this thesis reflect the diversity of cannabinoid pharmacology in the airways. They show for the first time that CBD has the ability to reduce antigen-induced bronchoconstriction, indicating relevance in bronchial asthma.